Hashimoto S, Kigoshi S, Muramatsu I
Department of Pharmacology, Fukui Medical School, Japan.
Eur J Pharmacol. 1993 Feb 9;231(2):209-14. doi: 10.1016/0014-2999(93)90451-m.
In the presence of adrenergic and cholinergic blocking agents, transmural electrical stimulation evoked a relaxation in isolated dog urethra precontracted with histamine. The response was abolished by tetrodotoxin, indicating its neurogenic origin. The non-adrenergic and non-cholinergic relaxation developed rapidly and was transient at low stimulation frequencies (< or = 1 Hz). However, at higher frequencies (> or = 5 Hz) the recovery phase of the relaxation became slow and often showed a notch, suggesting the presence of transient and slow components. NG-Monomethyl-L-arginine, a nitric oxide synthase inhibitor, inhibited the transient relaxation but did not affect the relaxation evoked at high stimulation frequencies. NG-Nitro-L-arginine, a more potent nitric oxide synthase inhibitor, abolished the transient relaxation produced at low stimulation frequencies and markedly attenuated the transient component at high frequencies. However, NG-nitro-L-arginine did not affect the slow component. The inhibition by NG-monomethyl-L-arginine and NG-nitro-L-arginine was reversed by the addition of L- but not D-arginine. Exogenously applied vasoactive intestinal polypeptide (VIP) produced a slowly developing relaxation. The slow relaxation induced by transmural electrical stimulation and VIP was not affected by [4-Cl-D-Phe6,Leu17]VIP, a reportedly competitive VIP antagonist. NG-Nitro-L-arginine did not affect the relaxation induced by VIP and sodium nitroprusside. These results suggest that the non-adrenergic and non-cholinergic relaxation induced by transmural electrical stimulation is composed of nitric oxide-dependent and -independent components in the isolated dog urethra.
在肾上腺素能和胆碱能阻断剂存在的情况下，经壁电刺激可使预先用组胺预收缩的离体犬尿道产生松弛。河豚毒素可消除该反应，表明其起源于神经源性。非肾上腺素能和非胆碱能松弛反应发展迅速，在低刺激频率（≤1Hz）时呈短暂性。然而，在较高频率（≥5Hz）时，松弛反应的恢复阶段变得缓慢，且常出现一个切迹，提示存在短暂性和缓慢成分。一氧化氮合酶抑制剂NG-单甲基-L-精氨酸可抑制短暂性松弛，但不影响高刺激频率时诱发的松弛。更有效的一氧化氮合酶抑制剂NG-硝基-L-精氨酸可消除低刺激频率时产生的短暂性松弛，并显著减弱高频率时的短暂性成分。然而，NG-硝基-L-精氨酸不影响缓慢成分。加入L-精氨酸而非D-精氨酸可逆转NG-单甲基-L-精氨酸和NG-硝基-L-精氨酸的抑制作用。外源性应用血管活性肠肽（VIP）可产生缓慢发展的松弛。据报道，竞争性VIP拮抗剂[4-氯-D-苯丙氨酸6，亮氨酸17]VIP不影响经壁电刺激和VIP诱导的缓慢松弛。NG-硝基-L-精氨酸不影响VIP和硝普钠诱导的松弛。这些结果表明，经壁电刺激诱导的非肾上腺素能和非胆碱能松弛在离体犬尿道中由一氧化氮依赖性和非依赖性成分组成。
